Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells

Phillips, David H.; Schoket, B.; Hewer, Alan; Bailey, E.; Kostic, S; Vincze, István

doi:10.1002/ijc.2910460403

Cited by 138 publications

(56 citation statements)

References 48 publications

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“…Some studies have found a linear correlation between adduct levels and daily or lifetime consumption of cigarettes (Phillips et al, 1988(Phillips et al, , 1990Dunn et al, 1991). Similar linear relationship was also found in bladder cancer biopsies.…”

Section: Dna Damage and Repairsupporting

confidence: 53%

Genetic susceptibility to tobacco-related cancer

et al. 2004

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Although cigarette smoking is the dominant risk factor for several epithelial cancers, only a small fraction of individuals with tobacco exposure develop cancer. The underlying hypothesis is that genetic factors may render certain smokers more susceptible to cancer than others. Genetic alterations in critical regulatory pathways may predispose cells to carcinogenesis. These pathways include regulation of xenobiotic metabolism; control of genomic stability, including DNA repair mechanisms, cell-cycle checkpoints, apoptosis and telomere length; and control of microenvironmental factors, such as matrix metalloproteinases, inflammation and growth factors. In addition, epigenetic events, such as promoter hypermethylation and loss of imprinting, are also involved in carcinogenesis. In this review, we will summarize recent advances in genetic susceptibility to tobacco-related cancer. Emphasizing on risk assessment, we will describe how genetic variations in the above-mentioned genetic pathways modify the tobacco-related cancer risk. In addition, we will discuss how genetic variations may assist in predicting clinical outcome, such as the natural history of cancer and treatment response. The measurements of genetic susceptibility by both genotypic and phenotypic assays are covered in the text. Finally, we present a number of current concerns that need to be addressed as the exciting field of molecular cancer epidemiology advances rapidly.

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Section: Dna Damage and Repairsupporting

confidence: 53%

Genetic susceptibility to tobacco-related cancer

et al. 2004

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“…A consistent finding is that levels of aromatic and hydrophobic adducts are significantly higher in smokers than in nonsmokers (9)(10)(11)(12)(13). In some studies, a linear correlation between estimated total or daily tobacco smoke exposure and adduct levels has been observed.…”

Section: Smoking-related Dna Adducts In Human Tissuesmentioning

confidence: 77%

DNA Adducts in Human Tissues: Biomarkers of Exposure to Carcinogens in Tobacco Smoke

Phillips¹

1996

Environmental Health Perspectives

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“…Studies on smokers and nonsmokers showed conflicting results on the effect of smoking on PAH-DNA adduct levels in WBC. Several studies did not reveal any significant differences in PAH-DNA adduct levels between the two groups Phillips et al, 1990;Van Maanen et al, 1994a), suggesting that adducts in WBC may result from other sources than tobacco smoking. In a study among roofers, PAH-DNA adduct levels in WBC correlated with the amount of PAH in skin wipes, but not with the amount of PAH in personal air samples, indicating that dermal contact might be a major route for DNA adduct formation in WBC (Herbert et al, 1990).…”

Section: Studies In Humansmentioning

confidence: 95%

A Critical Evaluation of DNA Adducts as Biological Markers for Human Exposure to Polycyclic Aromatic Compounds

Godschalk¹,

Schooten²,

Bartsch³

2003

BMB Reports

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The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention or chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria: i. adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined. iii. sources of interand intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAHexposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with nonexposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intraindividual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurements may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurements as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.

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Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells

Cited by 138 publications

References 48 publications

Genetic susceptibility to tobacco-related cancer

Genetic susceptibility to tobacco-related cancer

DNA Adducts in Human Tissues: Biomarkers of Exposure to Carcinogens in Tobacco Smoke

A Critical Evaluation of DNA Adducts as Biological Markers for Human Exposure to Polycyclic Aromatic Compounds

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